Nicolaou G, Chen A A, Johnston C E, Kenny G P, Bristow G K, Giesbrecht G G
Laboratory for Exercise and Environmental Medicine, Health, Leisure and Human Performance Research Institute, Winnipeg, Manitoba, Canada.
Can J Anaesth. 1997 Jun;44(6):636-42. doi: 10.1007/BF03015448.
This study was conducted to test the hypothesis that clonidine produces a dose-dependent increase in the sweating threshold and dose-dependent decreases in vasoconstriction and shivering thresholds.
Six healthy subjects (two female) were studied on four days after taking clonidine in oral doses of either 0 (control), 3, 6 or 9 micrograms.kg-1. The order followed a balanced design in a double-blind fashion. Oesophageal temperature and mean skin temperature (from 12 sites) were measured. Subjects were seated in 37 degrees C water which was gradually warmed until sweating occurred (sweat rate increased above 50 g.m-2.h-1). The water was then cooled gradually until thresholds for vasoconstriction (onset of sustained decrease in fingertip blood flow) and shivering (sustained elevation in metabolism) were determined. Thresholds were then referred to as the core temperature, adjusted to a designated mean skin temperature of 33 degrees C.
High dose clonidine similarly decreased the adjusted core temperature thresholds for vasoconstriction by 1.16 +/- 0.30 degrees C and for shivering by 1.63 +/- 0.23 degrees C (P < 0.01). The dose response effects were linear for both cold responses with vasoconstriction and shivering thresholds decreasing by 0.13 +/- 0.05 and 0.19 +/- 0.09 degree C.microgram-1 respectively (P < 0.0001). The sweating threshold was unaffected by clonidine, however the interthreshold range between sweating and vasoconstriction thresholds increased from control (0.19 +/- 0.48 degree C) to high dose clonidine (1.31 +/- 0.54 degrees C).
The decreases in core temperature thresholds for cold responses and increased interthreshold range are consistent with the effects of several anaesthetic agents and opioids and is indicative of central thermoregulatory inhibition.
本研究旨在验证可乐定可使出汗阈值呈剂量依赖性升高，使血管收缩阈值和寒战阈值呈剂量依赖性降低这一假说。
选取6名健康受试者（2名女性），在口服剂量分别为0（对照）、3、6或9微克·千克⁻¹的可乐定后，于4天内进行研究。研究顺序采用双盲法的平衡设计。测量食管温度和平均皮肤温度（来自12个部位）。受试者坐在37摄氏度的水中，水温逐渐升高直至出汗（出汗率超过50克·平方米⁻¹·小时⁻¹）。然后逐渐冷却水温，直至确定血管收缩（指尖血流持续下降开始）和寒战（代谢持续升高）的阈值。阈值随后被换算为核心温度，并调整至指定的平均皮肤温度33摄氏度。
高剂量可乐定同样使调整后的血管收缩核心温度阈值降低1.16±0.30摄氏度，使寒战核心温度阈值降低1.63±0.23摄氏度（P<0.01）。血管收缩和寒战阈值这两种冷反应的剂量反应效应均呈线性，分别降低0.13±0.05和0.19±0.09摄氏度·微克⁻¹（P<0.0001）。出汗阈值不受可乐定影响，但出汗与血管收缩阈值之间的阈值范围从对照时的（0.19±0.48摄氏度）增加至高剂量可乐定时的（1.31±0.54摄氏度）。
冷反应的核心温度阈值降低以及阈值范围增加与几种麻醉剂和阿片类药物的作用一致，表明存在中枢体温调节抑制。
